The cadherins are transmembrane receptors which function in a calcium- dependent, homophilic manner as one the primary mediators of cell-cell interactions. They cadherins belong to a large family of cell-cell adhesion molecules. Members of this family known as the classical cadherins are the primary components of adherens junctions. Their temporal expression has been shown to regulate the cell sorting events necessary for tissue development. The function of the classical cadherins in the developmental process is likely to depend, in part, on the regulation of their interaction with the unique cytoskeletal and signaling proteins, the catenins, which interact with their cytoplasmic domain and link the cadherins to the cytoskeleton. Despite their documented importance to numerous developmental systems, little is known about either the expression of cadherins and catenins or their role during salivary gland development. In order to map the adhesive interactions involved in the initiation and maintenance of salivary cell differentiation, we propose to examine the temporal and spatial distribution of cadherins, and their associated catenins, in the developing mouse submandibular gland (SMG). In addition, we plan to initiate functional studies by perturbing the expression of these adhesive molecules and assessing the cellular consequences. The specific aims are: Specific Aim 1. Determining which cadherins could function to control SMG differentiation. Specific Aim 2. Determining whether the composition of the cadherin-catenin complex is regulated with SMG development. Specific Aim 3. Examining of the hypothesis that cadherins regulate salivary gland differentiation by perturbing their expression and function.